Exenatide
| Exendin-4 ( Heloderma suspectum ) | ||
|---|---|---|
| Mass / length primary structure | 39 amino acids | |
| Precursor | (61 aa) | |
| Identifier | ||
| External IDs |
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| Drug information | ||
| ATC code | A10 BX04 | |
| DrugBank | DB01276 | |
| Drug class | Antidiabetic drugs | |
| Occurrence | ||
| Homology family | Exendin | |
| Parent taxon | Heloderma | |
Exenatid (trade name: Byetta , manufacturer: Lilly) is biotechnologically produced Exendin-4, a polypeptide that was found in the saliva of the North American Gila lizard ( Heloderma suspectum ). It was approved in 2005 as the first substance in the class of incretin mimetics (GLP-1 agonists) as a drug for lowering blood sugar in diabetes mellitus.
Therapeutic aspects
pharmacology
The structure of the peptide is similar to the human hormone glucagon-like peptide 1 (GLP-1). This small intestinal hormone , which is released after a meal, stimulates the release of the blood sugar-lowering hormone insulin in the β cells of the pancreas (see also incretin effect ). Like Exendin-4, exenatide consists of 39 amino acids with an additional C-terminal amide group . It has a direct blood-sugar-lowering effect by stimulating insulin secretion in a glucose-dependent manner and reducing the release of the insulin counterpart glucagon . It is broken down less quickly in the body than human GLP-1 and is therefore effective for longer.
Admission status
Exenatide has been approved as a drug under the trade name Byetta in the USA since 2005 . In 2006 it was approved by the European Commission and in 2007 Byetta was launched in Germany. In 2011, a (retard) form of exenatide that was only injected once a week was approved in Europe under the name Bydureon .
Application and effect
Due to its chemical structure, exenatide is not absorbed when administered orally, but has to be injected (subcutaneously). It is used in the treatment of type 2 diabetes as an alternative or as a complementary therapy when the sole use of oral antidiabetic drugs cannot achieve adequate blood sugar control or oral drugs cannot be tolerated. Exenatide is given subcutaneously approximately 30 to 60 minutes before a meal . In addition to lowering blood sugar, it delays gastric emptying, reduces appetite and increases the feeling of satiety. Since the effect depends on the blood sugar level, there is only a small risk of hypoglycaemia . The weight loss is independent of the occurrence of gastrointestinal side effects such as nausea or vomiting.
rating
In 2008 the Federal Joint Committee (G-BA) published a therapeutic advice on treatment with exenatide. In it, the G-BA informs about the scope of the approval as well as about the effect, effectiveness and risks, gives recommendations on the economic method of prescribing, the costs and any necessary precautionary measures for the prescription.
Adverse effects (side effects)
The most common side effects are gastrointestinal disorders such as nausea , vomiting and diarrhea , which occur in around half of the patients at least once during treatment . The severity of this is mild to moderate in most patients and depends on the dosage. The frequency and severity of these side effects decrease over the course of therapy. Other common side effects are headache , dizziness , temporary weakness and restlessness.
Isolated reports of the occurrence of acute pancreatitis under exenatide could not be safely attributed to the drug in studies.A retrospective study published in 2010 found no increased risk of acute pancreatitis under exenatide, but a generally increased risk of developing one in diabetics acute pancreatitis.
In 2011, the Drugs Commission of the German Medical Association (AKdÄ) informed about two cases in which pancreatic cancer was diagnosed in patients treated with exenatide . The AkdÄ only recommended the use of exenatide in special situations. Studies on the relationship between GLP1 agonists, the similar DPP4 inhibitors and cancer risk are contradicting.
The development of antibodies against exenatide is documented, but it is not known whether these lead to long-term tolerance development . Acute immunological reactions such as an anaphylactic defense reaction have been observed very rarely.
Trade names
Bydureon (sustained release formulation), Byetta
Web links
- www.medknowledge.de: Inkretin-Mimetika Exenatid (Byetta) vs. Lantus (insulin glargine) for diabetes
- www.prous.com: Molecule of the Month: Exenatide (Engl.)
literature
- Monthly medical magazine for pharmacists 3/06.
- Bray, GM (2006): Exenatide. In: Am J Health Syst Pharm . 63 (5): 411-418. PMID 16484515 .
- R. Göke, HC Fehmann, T. Linn, H. Schmidt, M. Krause, J. Eng, B. Göke: Exendin-4 is a high potency agonist and truncated exendin (9-39) amide a potent agonist at the GLP -1 (7-37) amide receptor of insulin-secreting β-cells. J. Biol. Chem. 1993; 268: 19650-19655. PMID 8396143 .
Individual evidence
- ↑ Entry on Exenatide in the DrugBank of the University of Alberta , accessed November 18, 2019.
- ↑ JJ Neumiller: differential chemistry (structure), mechanism of action, pharmacology and of GLP-1 receptor agonists and DPP-4 inhibitors. In: Journal of the American Pharmacists Association Volume 49 Suppl 1, 2009 Sep-Oct, pp. S16-S29, doi : 10.1331 / JAPhA.2009.09078 (currently unavailable) . PMID 19801361 .
- ↑ F. Folli, R. Guardado Mendoza: Potential use of exenatide for the treatment of obesity. In: Expert Opinion on Investigational Drugs . Volume 20, number 12, December 2011, pp. 1717-1722, doi : 10.1517 / 13543784.2011.630660 . PMID 22017240 . PMC 3495586 (free full text).
- ↑ Press release: Federal Joint Committee adopts therapeutic advice on exenatide and palivizumab . g-ba.de. June 20, 2008. Retrieved August 1, 2012.
- ↑ Garg R et al. Acute pancreatitis in type 2 diabetes treated with exenatide or sitagliptin: A retrospective observational pharmacy claims analysis. Diabetes Care 2010 Nov; 33: 2349; PMID 20682680 .
- ↑ Pancreatic carcinoma in connection with exenatide (Byetta®) (from the ADR database) . akdae.de. May 13, 2011. Retrieved August 1, 2012.
- ↑ German Diabetes Society: Statement on the work of Butler and colleagues on histological changes in the human pancreas after therapy with incretin-based drugs ( memento of the original from March 6, 2014 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. . DDG 2013, accessed March 6, 2014.
